The Effects of Chronic Restraint Stress on Innate and Adaptive Immune Responses to Acute Theiler?s Murine Encephalomyelitis Virus Infection ? An Animal Model of Human Multiple Sclerosis

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dc.contributorWelsh, C. Jane R.
dc.creatorSteelman, Andrew Jonathan
dc.date.accessioned2010-01-15T00:10:36Z
dc.date.accessioned2010-01-16T00:48:19Z
dc.date.accessioned2017-04-07T19:55:28Z
dc.date.available2010-01-15T00:10:36Z
dc.date.available2010-01-16T00:48:19Z
dc.date.available2017-04-07T19:55:28Z
dc.date.created2008-05
dc.date.issued2009-05-15
dc.description.abstractMultiple sclerosis (MS) is an immune-mediated prevalent chronic demyelinating and neurodegenerative disease of the central nervous system that begins with an abrupt onset during early adulthood. MS is idiopathic, but many factors are thought to influence the pathogenesis of the disease, which include genetic, gender and environmental factors. To date, there is much evidence that suggest that both the onset and progression of MS is facilitated by both viral infections and stress. Theiler?s murine encephalomyelitis virus (TMEV) is a picornavirus that upon inoculation into susceptible strains of mice (i.e. SJL and CBA) causes a persistent infection which, in turn, results in an early acute encephalomyelitis followed by a late chronic immune-mediated demyelinating and neurodegenerative disease that pathologically resembles MS. In contrast, resistant mice (i.e C57BL/6 and BALB/c) are able to clear the virus from the CNS, and consequently do not develop chronic demyelination. Previous studies indicated that stress during early infection of susceptible mice can increase CNS viral titers and alter dissemination of TMEV, decrease early cytokine and chemokine expression in the spleen and CNS, and result in an exacerbated late demyelinating disease. The studies herein, focused on the hypothesis that chronic stress during early infection with TMEV infection would lead to drastic immunosuppression of both innate and adaptive arms of immunity, and that this immunosuppression may overcome the genetically controlled resistance of C57BL/6 mice to Theiler?s virus-induced demyelination. In these series of studies, we were able to show that stress, regardless of mouse strain susceptibility, decreases NK cell activity, and increased viral titers at day 1 p.i. Furthermore, after seven days of stress, susceptible mice demonstrated decreased virus specific T-cell effector function in both the CNS and spleens as indicated by a globalized reduction in type 1 and type 2 cytokines, as well as transcription factors. Importantly, these decreased responses were, in part, attributable to the actions of glucocorticoids. However, stress during early infection of C57BL/6 mice did not alter resistance to demyelination. These results begin to shed light on how stress, infection, and genetics can influence the onset of human MS.
dc.identifier.urihttp://hdl.handle.net/1969.1/ETD-TAMU-2661
dc.language.isoen_US
dc.subjectTheiler's virus
dc.subjectMultiple Sclerosis
dc.subjectRestraint stress
dc.subjectT-cell
dc.subjectB-cell
dc.subjectImmune response
dc.titleThe Effects of Chronic Restraint Stress on Innate and Adaptive Immune Responses to Acute Theiler?s Murine Encephalomyelitis Virus Infection ? An Animal Model of Human Multiple Sclerosis
dc.typeBook
dc.typeThesis

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